INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The swallowing reflex functions to minimize the risk of aspiration of foreign materials into the respiratory tract (1). Constriction of the pharynx ensures completion of swallowing while the patent pharynx is mandatory for breathing. Thus, there must be some precise coordination between swallowing and respiration, although the underlying mechanisms have not been completely elucidated (2).

In a previous study (3), we showed that as the level of nasal constant positive airway pressure (CPAP) increased, the latency of the swallowing reflex response following bolus injections of distilled water was progressively prolonged, and that the number of swallows elicited by continuous infusion of water progressively decreased. We speculated about two possible mechanisms for the observation: (1) alteration of upper airway receptor function responsible for swallowing, and (2) lung-volume-related inhibitory reflex for swallowing. Wilson and colleagues (4) reported that in human infants the interval between airway closure and the onset of the subsequent inspiratory effort was generally longer when the swallow occurred at high lung volumes. Their observation suggests the presence of an interaction between swallowing reflex and lung volume. No study, to our knowledge, has explored direct influence of lung volume changes on swallowing reflex. Accordingly, we tested the hypothesis that lung inflation modulates the swallowing reflex. We evaluated the coordination of respiration and swallowing in response to lung volume changes produced by application of negative extrathoracic pressure (NEP) in awake human subjects.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The research was carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association. After obtaining approval from the Institutional Ethics Committee and informed consent, 11 healthy volunteers aging 24 to 42 yr (six men and five women) were studied. All subjects were told about the various procedures that would take place but none was familiar with the hypothesis being tested.

Preparation of Subjects

Each subject was rested in a supine position and wore a plastic extrathoracic shell covering the anterior part of the chest for producing NEP by a pressure control system (5). We measured ventilatory airflow with a pneumotachograph, and tidal volume (VT) was obtained by electrical integration of the expired flow signal. End-tidal CO₂ tension (PET_CO2) was monitored with an infrared CO₂ analyzer through a port in a tightly fitting facemask. Swallowing was determined by a burst of submental electromyogram EMG (EMGSM) with interruption of airflow. Reflex swallows were induced by a bolus injection of distilled water (1 ml) during early expiration without knowledge of the subject or continuous infusion of water (3 ml/min) into the pharynx through a thin nasopharyngeal catheter placed without the use of topical anesthesia as we previously described (6, 7).

Lung Volume Changes

Three different levels of lung inflation were achieved by random applications of NEP0 (control), 20 (NEP20), and 40 cm H₂O (NEP40). Before the swallowing study, the tightly fitted facemask was connected to a water-sealed spirometer, and changes in the functional residual volume (FRC) by each NEP were measured with a sudden withdrawal of the NEP.

Experimental Protocol

All subjects were accustomed to the applied NEP and to a bolus and continuous infusion of water into the pharynx before the measurements. For each preselected NEP level, five trials of a bolus injection of water were performed randomly with a minimum interval of 2 min, and the responses to continuous infusion of water were measured for 3 min after confirming 4-5 min steady-state breathing pattern. Measurements were randomly repeated at three different NEPs.

Data Analysis

The response to bolus injections of water was analyzed in terms of latency of the response, which was calculated from the time of bolus injection identified by increase in pressure of the nasopharyngeal catheter (PCAT) to the onset of the first swallowing identified by the EMGSM. After rejecting maximum and minimum values of the latency, three results were averaged in each subject.

The response to continuous infusion of water was analyzed using the data of the last 2 min of a 3-min period of water infusion. In addition to respiratory rate, VT, and minute ventilation, which is the product of respiratory rate and VT, the number of swallows elicited during the period was calculated. Furthermore, the timing of the swallows in relation to the phase of the respiratory cycle was determined as described previously (6, 7).

Statistical analysis was performed by using Kruskal-Wallis one-way analysis of variance (ANOVA) on ranks, followed by Dunnet's test. Data are expressed as median (range).

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Eleven subjects completed the experimental protocol. None showed a sign of laryngeal irritation such as coughing during the experiment.

Responses to Bolus Injection of Water

A total of 165 swallows in 11 subjects were analyzed. Figure 1 shows representative recordings of swallows elicited by bolus injections of water during control and NEP40 conditions. As clearly illustrated by the figure, the latency was markedly prolonged during the load of NEP40. There was a dose-dependent prolongation of the latency in response to increases in the level of NEP (Figure 2).

View larger version (12K): [in this window] [in a new window]   Figure 1.   Changes in the latency of response to bolus infusion in water at the control condition and NEP40. Arrow indicates instant of injection of water.

View larger version (10K): [in this window] [in a new window]   Figure 2.   Changes in the latency of response to bolus infusion in water at the control condition, NEP20, and NEP40. The box plot data show the median, interquartile range, and 10th and 90th percentiles. (Open circles) Data outside the 10th-90th percentile intervals. *p < 0.05, significantly different from control.

Responses to Continuous Infusion of Water

A total of 353 swallows in 11 subjects were analyzed. Table 1 summarizes changes in respiratory frequency, tidal volume, minute ventilation, PET_CO2 for each of the NEP levels before and during infusion of water, and increases in FRC in response to the NEPs. Respiratory rate, tidal volume, minute ventilation, and PET_CO2 were not significantly influenced by application of NEP both before and during infusion of water.

As demonstrated by typical recordings of responses to continuous infusion of water during control and NEP40, the rate of swallows markedly decreased during NEP40 (Figure 3). It should also be noted that the subject swallowed mainly during the expiratory phase during control measurement whereas no such predominant phase of swallows was observed during the load of NEP40. As shown by Figure 4, the frequency of swallows significantly decreased as the level of NEP increased. Distribution of the timing of swallows in reference to the phase of the respiratory cycle was markedly changed during NEPs as illustrated in Figure 5. The expiratory swallows observed most commonly during the control condition significantly decreased during the loads of NEP20 and NEP40, and swallows at the E-I transition phase significantly increased with increasing levels of NEP. These changes in distribution of the timing of swallows indicate that the preponderant coupling of swallows with the expiratory phase can be lost with application of NEP.

View larger version (21K): [in this window] [in a new window]   Figure 3.   Changes in swallowing response to continuous infusion in water at the control condition and NEP40 (VT = tidal volume; PETCO2 = end tidal PCO2; EMGSM = submental electromyogram).

View larger version (12K): [in this window] [in a new window]   Figure 4.   Changes in the frequency of swallows at the control condition, NEP20, and NEP40. The box plot data show the median, interquartile range, and 10th and 90th percentiles. (Open circles) Data outside the 10th-90th percentile intervals. *p < 0.05, significantly different from control.

View larger version (18K): [in this window] [in a new window]   Figure 5.   Distribution of timing of swallows in relation to the phase of the respiratory cycle during continuous infusion of water at three different lung volumes. The percentage of swallows coinciding with each phase of the respiratory cycle was calculated for individual subjects. The box plot data show the median, interquartile range, and 10th and 90th percentiles. (Open circles) Data outside the 10th-90th percentile intervals. *p < 0.05, significantly different from control for a given timing of swallow.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

In the present study, we found that (1) an increase in lung volume produced by NEP prolongs the latency of swallow following a bolus injection of water into the pharynx, (2) an increase in lung volume decreases the rate of swallowing during continuous infusion of distilled water into the pharynx, and (3) the timing of swallows in the phase of the respiratory cycle can be modified by changes in lung volume.

Limitations of the Study

Although we designed the study only to examine the influence of lung volume change on the swallowing reflex, several uncontrolled factors might have affected the results of the study. For example, the extrathoracic shell covered both the abdominal cage and thoracic cage, and application of NEP expanded the abdominal cage more than the thoracic cage as the former is more compliant than the latter. It is possible that abdominal and chest wall deformation might have influenced mechanically the swallowing act. Also, the abdominal and chest wall deformation due to NEP may possibly stimulate the mechanoreceptors within the abdominal and intercostal muscles and modulate the reflexively swallowing reflex. In addition, even though NEP does not directly influence the upper airway, it possibly has indirect effects that may play a role in modulation of the swallowing reflex. For example, increases in lung volume due to NEP can cause an increase in tracheal traction on the upper airway, stiffening and dilating this structure. Therefore, the results do not exclude that the effect on swallowing is due to alterations in the upper airway. Furthermore, some subjects reported an uncomfortable, stuffy sensation around the chest during NEP. Thus, discomfort induced by NEP application may possibly change the coordination of respiration and swallowing.

Mechanisms of Depression of Swallowing Reflex during Lung Inflation

The findings that NEP prolonged the swallowing latency following bolus water injection and decreased the frequency of swallows during continuous infusion of water into the pharynx indicate that NEP attenuates the swallowing reflex. The mechanisms of this attenuation of swallowing reflex are not clear. However, considering that NEP produces lung inflation and chest wall deformation, we can speculate that the attenuation of the swallowing reflex during NEP is associated with vagally mediated lung reflex or other chest wall reflex. In this connection, it has been suggested that the inhibition of the swallowing reflex may occur at the central nervous system, particularly at the internuncial level where the interneurons link both afferent and efferent limbs of the swallowing reflex (2). Thus, the nucleus tractus solitarius (NTS) is considered to be the most important site for elicitation and control of the swallowing reflex as the NTS is not only an afferent portal but has interneurons that perform a very complex level of swallowing control. In fact, control over the rate of reflexively induced swallowing occurs in the intermediate network at the level of NTS (6). Because afferent inputs from vagally mediated lung receptors terminate within the NTS, it is plausible that lung inflation may produce an input that is inhibitory to the swallowing reflex elicited by water instillation into the pharynx. In our study no consistent changes in respiratory variables were observed even during the application of NEP40 that caused an increase in lung volume of 0.4-0.9 L above FRC, suggesting that this level of NEP did not set up the Breuer-Hering inflation reflex. Therefore, the observed attenuation of the swallowing reflex during lung inflation may be independent of the Breuer-Hering inflation reflex.

Our previous study demonstrated that nasal CPAP attenuates the swallowing reflex in conscious human subjects (3). Because nasal CPAP may cause not only lung volume changes but also mechanical deformation of the pharyngeal and laryngeal airways, the attenuation of swallowing reflex during nasal CPAP may not be explained only by the inhibitory influence of lung inflation on the swallowing reflex. Nevertheless, it is very likely that such inhibitory influence of lung inflation plays a significant role in the depression of the swallowing reflex during nasal CPAP.

Influence of Lung Volume on Swallowing Timing

In this study, we found that application of NEP caused a shift of swallows occurring in the expiratory phase to later times in the respiratory cycle, which resulted in a loss of the preponderant coupling of swallows with the expiratory phase. Although the attenuation of the swallowing reflex may contribute to the change of swallowing timing, the exact mechanisms that cause the shift of the timing of swallows in response to lung inflation are unclear. A similar change in the timing of swallows has been observed during hypercapnia (7) and with the addition of respiratory elastic loading (5). Lung inflation due to NEP may cause mechanical disadvantage of the inspiratory muscles, owing to the length-tension characteristics that depend on lung volumes, which in turn cause an increase in central respiratory drive to maintain an adequate ventilation. An interruption of airflow by the act of swallowing in the presence of increased ventilatory drive may incur an additional burden to the respiratory control system. Thus, it is conceivable that there may be an active mechanism that controls the coupling of swallowing with the phases of respiration so that there is adequate ventilation with minimum disturbance of airflow during repetitive swallowing in response to any respiratory loading. Such a mechanism may cause the preferential occurrence of E-I swallows during NEP as it is clear that swallows occurring in the E-I transition caused little or no effect on the airflow of ongoing respiration. It has also been reported that the pressure gradient between the hypopharynx and the upper esophagus sphincter is greater during expiration than during inspiration (9), indicating that the act of swallowing uses more energy during expiration than during inspiration. The shift of swallows from the expiratory period to the E-I period may be beneficial for conservation of energy used for repetitive swallowing in response to the increased effort of breathing.

It has been suggested that swallows during the E-I transition phase are the most liable to produce aspiration (10). However, in the present study the incidence of laryngeal irritation did not increase despite the fact that the occurrence of E-I transition swallows increased during NEP application. The absence of laryngeal irritation in the face of the increased occurrence of E-I swallows during NEP may be due partly to the fact that NEP increases the pressure gradient between the hypopharynx and the upper esophagus when the esophagus sphincter opens and thus causes an effective swallowing.

In conclusion, our results support the hypothesis that lung inflation modulates the swallowing reflex. This modulation of swallowing reflex is compatible with a notion that the automatic respiratory control system prevails over the swallowing reflex when the maintenance of ventilation with minimum disturbance of airflow is particularly important in a condition of increased respiratory loading.